pISSN 2671-8790 eISSN 2671-8804

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Review Article

J Korean Soc Transplant 2017; 31(4): 157-169

Published online December 31, 2017

https://doi.org/10.4285/jkstn.2017.31.4.157

© The Korean Society for Transplantation

Current Perspectives on Emerging CAR-Treg Cell Therapy: Based on Treg Cell Therapy in Clinical Trials and the Recent Approval of CAR-T Cell Therapy

Koeun Kang1, Junho Chung, M.D.1, Jaeseok Yang, M.D.2,3 and Hyori Kim, Ph.D.4

Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine1, Transplantation Center2, Department of Surgery3, Seoul National University Hospital, Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center4, Seoul, Korea

Correspondence to: Hyori Kim
Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Tel: 82-2-3010-5825, Fax: 82-2-3010-4182 E-mail: hyorikim@amc.seoul.kr

Received: October 26, 2017; Accepted: October 30, 2017

Abstract

Regulatory T cells (Treg) naturally rein in immune attacks, and they can inhibit rejection of transplanted organs and even reverse the progression of autoimmune diseases in mice. The initial safety trials of Treg against graft-versus-host disease (GVHD) provided evidence that the adoptive transfer of Treg is safe and capable of limiting disease progression. Supported by such evidence, numerous clinical trials have been actively investigating the efficacy of Treg targeting autoimmune diseases, type I diabetes, and organ transplant rejection, including kidney and liver. The limited quantity of Treg cells harvested from peripheral blood and subsequent in vitro culture have posed a great challenge to large-scale clinical application of Treg; nevertheless, the concept of CAR (chimeric antigen receptor)-Treg has emerged as a potential resolution to the problem. Recently, two CAR-T therapies, tisagenlecleucel and axicabtagene ciloleucel, were approved by the US FDA for the treatment of refractory or recurrent acute lymhoblastic leukemia. This approval could serve as a guideline for the production protocols for other genetically engineered T cells for clinical use as well. The phase I and II clinical trials of these agents has demonstrated that genetically engineered and antigen-targeting T cells are safe and efficacious in humans. In conclusion, both the promising results of Treg cell therapy from the clinical studies and the recent FDA approval of CAR-T therapies are paving the way for CAR-Treg therapy in clinical use.

Keywords: Transplantation, Rejection, Autoimmune disease, Regulatory T cells, Chimeric antigen receptor